Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed continuous infusion (CI) of fludarabine and cytarabine (FLAG) plus idarubicin for patients under 60-years old with resistant acute myeloid leukemia (AML). Induction chemotherapy consisted of idarubicin (12 mg/m(2) iv infusion over 30 min on Days 1-3), plus fludarabine (30 mg/m2/day) and cytarabine (1,000 mg/m(2)/day) on Days 1-5 as a 24-hr CI. G-CSF was added on Days 1-5. The 29 patients enrolled were of median age 40 years (range, 18-57 years); of these, 8 (27.6%) had primary refractory disease, 19 (65.5%) were in early relapse, and 1 each (3.4%) was in multiple relapse and relapse after SCT. In response to induction, 8 patients (27.6%) achieved CR, 2 (6.9%) achieved CRp, and 19 (65.5%) failed treatment; of the latter, 14 had aplasia, three had an indeterminate course, and two showed resistance. Seven patients remain alive, while two were lost to follow-up. Nineteen patients died, 14 of infection, one of toxicity during consolidation, three of relapse after SCT, and two of persistent disease. These findings indicate that although CI of FLAG plus idarubicin was effective for eradicating blasts, it carried a high risk of toxicity. Reduced doses are recommended for CI of FLAG plus idarubicin.
 ...
PMID:Continuous infusion of intermediate-dose cytarabine and fludarabine with idarubicin for patients younger than 60 years with resistant acute myeloid leukemia: a prospective, multicenter phase II study. 1919 34

The cancer stem cell (CSC) hypothesis suggests that clonogenic growth potential within an individual tumor is restricted to a specific and phenotypically defined cell population. Evidence for CSC in human tumors initially arose from studies of AML, but functionally similar cell populations have been identified in an increasing number of malignancies. Despite these findings, controversy surrounds the CSC hypothesis, especially the generalization that clonogenic tumor cells are rare. Nevertheless, efforts to define the cellular processes regulating self-renewal and resistance to anticancer therapeutics, two of the major properties ascribed to CSC, are likely to provide useful insights into tumor biology as a whole. BMT has been at the forefront of clinically translating basic stem cell concepts starting with the original hypothesis that normal hematopoietic precursors could rescue patients from myeloablative doses of radiation or chemotherapy. Even today, a better understanding of CSC may enhance ongoing efforts to induce specific and effective anti-tumor immune responses in both the allogeneic and autologous setting. It is also likely that new clinical research approaches will be required to accurately evaluate novel CSC-targeting strategies. Owing to the capacity to produce remissions in most diseases, SCT may provide the ideal clinical platform to carry out these investigations by studying the ability of anti-CSC agents to prolong relapse free and overall survival.
 ...
PMID:Cancer stem cells: relevance to SCT. 1923 7

We examined whether the use of G-CSF-primed unmanipulated bone marrow (pBM) permits successful transplantation in patients with adverse comorbid pretransplantation conditions. A total of 33 patients at variable risk of AML undergoing allogeneic SCT from an HLA-identical sibling participated. The patients suffered from a variety of treatment-related sequelae before SCT and many cases also featured the presence of major organ dysfunction. The median follow-up duration of patients who were among the overall survivors was 58 months (range, 11-125 months). The median number of CD34(+) cells infused was 3.5 x 10(6) per kg (range, 0.8-15.6 x 10(6) per kg). The median number of days for recovery of ANC and platelet count without transfusion was 13 (range, 6-22) and 18 (range, 11-29) days, respectively. Four patients (12%) died due to nonrelapse causes and only one patient developed the same course of infectious complication as before SCT. No particular finding in the context of CMV infection or other post transplant complication was observed. The estimated 10-year overall survival rate was 68%. Our results suggest that the use of pBM allows successful engraftment without increasing complications in patients with various comorbidities before transplantation.
 ...
PMID:Overcoming various comorbidities by G-CSF-primed unmanipulated BM SCT in adult patients with AML. 1927 Jul 28

We studied the feasibility and efficacy of a two-step approach to Auto-SCT for patients with AML in second remission. Step 1 consisted of consolidation chemotherapy using cytarabine 2000 mg/m(2) i.v. every 12 h for 4 days plus etoposide 40 mg/kg total dose by continuous i.v. infusion over the same 4 days. PBSC were collected after G-CSF stimulation during recovery from this chemotherapy. Step 2, auto-SCT, used a preparative regimen of oral BU 16 mg/kg over 4 days followed by etoposide 60 mg/kg i.v. Of the 50 patients entered on Step 1, two died from treatment complications, and seven failed to proceed to transplantation. A median CD34+ cell dose of 5.9 x 10(6)/kg was collected in a median of three collections. With a median follow-up of 8.2 years, 5-year disease-free survival (DFS) is 28%. The most important prognostic factor was cytogenetics, with acute promyelocytic leukemia (APL) patients having a 5-year DFS of 67% compared with 16% for others. We conclude that this two-step approach to autologous transplantation produces good CD34+ mobilization and that this approach has cured some patients. Results in patients with APL are especially promising.
 ...
PMID:Auto-SCT for AML in second remission: CALGB study 9620. 1928 99

The aim of this multicenter retrospective analysis was to carry out a survey of overall outcomes after allo-hematopoietic SCT of AML patients harboring trisomy 8 (+8) as the sole chromosomal abnormality or associated with other abnormalities. We have identified 182 de novo AML patients who underwent allo-hematopoietic SCT between 1990 and 2007 exhibiting isolated +8 (n=136) or +8 (n=46) associated with other favorable (n=8), intermediate (n=30), high-risk (n=7) or unknown (n=1) cytogenetic abnormalities reported to the European Group of Blood and Marrow Transplantation (EBMT). With a median follow-up of 48 months, 5-year non-relapse mortality, relapse rate, leukemia-free survival and OS were 25, 30, 45 and 47%, respectively. In a multivariate analysis, leukemia-free survival rate was improved when patients were female and transplanted in CR with an HLA-identical sibling donor. Five-year leukemia-free survival was 41, 88, 57 and 21% in patients bearing isolated +8 or +8 and other cytogenetic abnormalities of good, intermediate or poor-risk, respectively. Our retrospective data show that allo-hematopoietic SCT is an effective treatment for AML patients harboring +8. The accompanying cytogenetic abnormality to +8 seems to influence outcomes of these patients.
 ...
PMID:Outcome after allogeneic transplantation for adult acute myeloid leukemia patients exhibiting isolated or associated trisomy 8 chromosomal abnormality: a survey on behalf of the ALWP of the EBMT. 1934 53

Owing to the heterogeneity of AML, the indication for allogeneic SCT (allo-SCT) requires an exact definition of the individual subentity and risk category. A comprehensive diagnostic approach is needed, which combines cytomorphology, cytogenetics, FISH, molecular genetics and immunophenotyping. Whereas the categorization in three prognostic karyotype groups is well established, rare recurrent aberrations as the unfavorable t(8;16)(p11;p13), inv(3)(q21q26) and t(6;9)(p23;q34) must also be considered. In normal karyotype, PCR analyses reveal prognostically relevant mutations in >85% of cases, and a molecular data set composed of the FLT3-ITD, MLL-PTD, NPM1 and CEBPA mutations was found able to guide the selection of patients for allo-SCT. Some novel markers as the WT1 mutations might further contribute to risk stratification in normal karyotype. The panel of minimal residual disease parameters is being expanded at this time, for example, by quantitative PCR for the NPM1 mutations. Immunophenotyping allows the definition of leukemia-associated phenotypes in nearly all cases, but its position in the indication to allo-SCT has to be validated. Thus, the optimization of the indication to allo-SCT is an ongoing process that should remain in continuous interaction with the increasing panel of known genetic markers and diagnostic methods.
 ...
PMID:Interactive diagnostics in the indication to allogeneic SCT in AML. 1936 29

In 1997-2003, a protocol for treatment of acute myeloid leukaemia (AML) (except promyelocytic leukaemia) was activated in four Swedish health care regions covering 50% of the national population. Based on cytogenetics and clinical findings, patients aged 18-60 yr were assigned to one of three risk groups. In this report we account for the long-term clinical outcome of enrolled patients. Patients received idarubicin and cytarabine in standard doses as induction therapy and consolidation courses included high-dose cytarabine. Allogeneic stem cell transplantation (allo-SCT) from an human leucocyte antigen-identical sibling was recommended in standard and poor-risk patients, whereas unrelated donor transplant was reserved for poor-risk patients. Autologous (auto-SCT) was optional for standard or poor risk patients not eligible for allo-SCT. Two hundred seventy-nine patients with de novo or secondary (9%) AML, median age 51 (18-60) yr, corresponding to 77% of all patients in the population, were included. Twenty (7%) patients were assigned to the good risk group, whereas 150 (54%) and 109 patients (39%) were assigned to standard- and poor-risk groups, respectively. Induction failures accounted for 55 patients; 16 early deaths eight of whom had white blood cell (WBC) >100 at diagnosis, and 39 refractory disease. Thus, complete remission (CR) rate was 80%. At study closure, the median follow-up time of living patients was 90 months. Median survival time from diagnosis in the whole group was 27 months and 4-yr overall survival (OS) rate was 44%. In good, standard, and poor risk groups, 4-yr OS rates were 60, 57 and 24%, respectively. Median relapse-free survival (RFS) time in CR1 was 25 months and RFS at 4 yr was 44%. Four-year RFS rates were significantly (P < 0.001) different between the three risk groups; 64% in good risk, 51% in standard risk and 27% in poor risk patients. One hundred-ten transplantations were performed in CR1; 74 allo-SCT (50 sibling, 24 unrelated donor), and 36 auto-SCT. Non-relapse mortality was 16% for allo-SCT patients. Outcome after relapse was poor with median time to death 163 d and 4-yr survival rate 17%. Three conclusions were: (i) these data reflect treatment results in a minimally selected population-based cohort of adult AML patients <60 yr old; (ii) a risk-adapted therapy aiming at early allogeneic SCT in patients with a high risk of relapse is hampered by induction deaths, refractory disease, and early relapses; and (iii) high WBC count at diagnosis is confirmed as a strong risk factor for early death but not for relapse.
 ...
PMID:Results of risk-adapted therapy in acute myeloid leukaemia. A long-term population-based follow-up study. 1938 87

Acute myeloid leukemia (AML) patients with internal tandem duplication (ITD) mutations in the Fms-like tyrosine-3 (FLT3) gene have a dismal prognosis. Here we report compassionate-use results with the multikinase and FLT3-ITD inhibitor sorafenib for the treatment of relapsed or refractory FLT3-ITD-positive AML. Sorafenib induced clinically meaningful and very rapid responses in all 6 patients treated either before (n = 2), after (n = 3), or both before and after (n = 1) allogeneic stem cell transplantation (allo-SCT). Sorafenib-induced remissions facilitated allo-SCT in 2 of the 3 refractory patients. Two of the 4 patients who were treated after allo-SCT survived 216 and 221 days, respectively, whereas the other 2 remain in ongoing complete molecular remission. Sorafenib response was associated with an inhibition of the antiapoptotic FLT3-ITD target Stat-5 in vivo. Together, sorafenib monotherapy before or after allo-SCT has remarkable clinical activity in poor risk FLT3-ITD-positive AML and deserves further evaluation in prospective clinical trials.
 ...
PMID:Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation. 2094 91

We earlier published data on 136 children who received hematopoietic SCT (HSCT) for ALL, and showed that early lymphocyte recovery is a powerful indicator for survival by GVL effect without increase in GVHD. To answer the question whether this is true for AML, we extended our cohort to 207 consecutive children with acute leukemia by adding 71 children with AML who received 75 HSCT's between 1994 and 2005. For the AML cohort, all patients at time of HSCT were in complete morphological remission (CR) except for one patient in CR1, who had 8% blasts in the BM before HSCT. All patients received myeloablative regimens. Stem cell sources were: matched sibling donor in 40 patients, mismatched related donor in eight patients, matched unrelated donor in 25 children and two children received cord progenitor stem cells. ALL results were published with significant P-values. In AML, absolute lymphocyte count <0.3 x 10(9)/l or >0.3 x 10(9)/l on days 21 and 30 were not predictive of relapse with a hazard ratio at day 21=0.88; P=0.8, and hazard ratio at day 30=0.5; P=0.2.
 ...
PMID:Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia-Update study. 1942 Nov 73

Haploidentical SCT (HaploSCT) has been most commonly performed using a myeloablative, TBI-based preparative regimen; however, the toxicity with this approach remains very high. We studied the feasibility of a reduced-intensity conditioning regimen in a phase II clinical trial using fludarabine, melphalan and thiotepa and antithymocyte globulin (ATG) for patients with advanced hematological malignancies undergoing T-cell depleted HaploSCT. Twenty-eight patients were entered in the study. Engraftment with donor-derived hematopoiesis was achieved in 78% of patients after a median of 13 days. Six patients experienced primary graft failure, three out of four tested patients had donor-specific anti-HLA antibodies (DSA) (P=0.001). Toxicity included mostly infections. A total of 21 out of 22 patients with AML/myelodysplastic syndrome (MDS) achieved remission after transplant (16 with relapsed/refractory AML). Five out of the 12 patients (42%) with AML/MDS with <15% BM blasts survived long term as compared with none with more advanced disease (P=0.03). HaploSCT with this fludarabine, melphalan and thiotepa and ATG RIC is an effective, well-tolerated conditioning regimen for patients with AML/MDS with low disease burden at the time of transplant and allowed a high rate of engraftment in patients without DSA. Patients with overt relapse fared poorly and require novel treatment strategies.
 ...
PMID:Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT. 1966 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>